Understanding the role of Pentraxin 3 in senescence and fibrogenesis in adipose tissue and liver during aging

Abstract

The inflammaging is defined as chronic and low-grade inflammation when aging. The pathogenesis of age-related diseases largely results from the development of inflammaging. Interestingly, patients with obesity share largely similar phenotypes with aging and both obesity and aging are accompanied by progressive inflammation in adipose tissue. Pentraxin 3 (PTX3) is a soluble pattern recognition receptor and plays an important role in the innate immune system. Moreover, PTX3 can be induced by different inflammatory stimuli in adipocytes. The change levels of plasma PTX3 has been observed in patients with metabolic diseases or aging individuals, however, investigating the role of PTX3 in adipose tissue and liver during inflammation and aging is still needed since the mechanism is not completely understood. My research is focused on understanding the role of PTX3 in senescence and fibrogenesis in adipose tissue and liver during aging. In the first project, we investigated the effect of PTX3 deficiency on cellular senescence and fibrogenesis of stromal vascular (SV) cells of brown adipose tissue (BAT) and inguinal (ING) white adipose tissue (Ing-WAT) from old female mice, and we found out that PTX3 deficiency results in increased senescence and fibrogenesis in SV cells of subcutaneous adipose tissue. In the second project, we determined the direct role of PTX3 in senescence and fibrogenesis by investigating the reversal effect of recombinant mouse PTX3 (rmPTX3) on senescence and fibrogenesis in SV cells. Unfortunately, we didn’t see the reversal effect of recombinant mouse PTX3 (rmPTX3) on senescence and fibrogenesis in SV cells. In the third project, we examined whether PTX3 deficiency impacts senescence and lipogenesis in liver in vivo, and we demonstrated that PTX3 deficiency itself significantly downregulated gene expression in lipogenesis, lipolysis, and mitochondria function in liver. Also, PTX3 deficiency attenuated fibrogenesis and gluconeogenesis in liver. In summary, my master research reveals that PTX3 deficiency results in increased senescence and fibrogenesis in SV cells of subcutaneous adipose tissue in old female mice and PTX3 deficiency attenuates lipid transport and oxidation, fibrogenesis, and gluconeogenesis in the liver.